Systemic Metabolic Alterations Correlate with Islet-Level Prostaglandin E2 Production and Signaling Mechanisms That Predict β-Cell Dysfunction in a Mouse Model of Type 2 Diabetes
Abstract
:1. Introduction
2. Results
2.1. Initial Observation That Metabolic Phenotype Can Be Indpendent of Genotype in the BTBRob Mouse Model of T2D
2.2. An Altered Gut Microbiota Composition Is Associated with T2D Resistance vs. Susceptiblity BTBROb Mice
2.3. The Gut Microbiota Composition of Normoglycemic BTBROb Mice Is Significantly Different Compared to Both T2D BTBROb and WT Controls, At Least Partially Independent of Diet
2.4. The T2D Phenotype Is Associated with Altered Circulating Incretin and Adipokine Levels
2.5. An Integrated Ultrahigh-Resolution FIE-FTCIR MS Metabolomics Approach Accurately Clusters Mouse Plasma Samples by Disease State
2.6. Diet Alone Does Not Explain the Phenotype of Male BTBRob Mice at 10 Weeks of Age
2.7. FIE-FTCIR MS Metabolomics Reveals That Elevations in Circulating Eicosanoid Precursors Correlate Directly with Agonist-Dependent EP3 Signaling in T2D β-Cell Dysfunction
3. Discussion
4. Materials and Methods
4.1. Animal Care and Husbandry
4.2. Blood Glucose Measurements and Insulin Tolerance Tests
4.3. Ex Vivo Islet Glucose Stimulated Insulin Secretion Assays
4.4. Quantitative PCR for Gene Expression Analyses
4.5. Terminal Blood Collection and Plasma Hormone/Metabolite Assays
4.6. Gut Microbial DNA Preparation, Sequencing, and Analysis
4.7. FIE-FTCIR MS for Unbiased Plasma Metabolomics
4.8. Statistical Analyses
4.9. Data Availability
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Schaid, M.D.; Zhu, Y.; Richardson, N.E.; Patibandla, C.; Ong, I.M.; Fenske, R.J.; Neuman, J.C.; Guthery, E.; Reuter, A.; Sandhu, H.K.; et al. Systemic Metabolic Alterations Correlate with Islet-Level Prostaglandin E2 Production and Signaling Mechanisms That Predict β-Cell Dysfunction in a Mouse Model of Type 2 Diabetes. Metabolites 2021, 11, 58. https://doi.org/10.3390/metabo11010058
Schaid MD, Zhu Y, Richardson NE, Patibandla C, Ong IM, Fenske RJ, Neuman JC, Guthery E, Reuter A, Sandhu HK, et al. Systemic Metabolic Alterations Correlate with Islet-Level Prostaglandin E2 Production and Signaling Mechanisms That Predict β-Cell Dysfunction in a Mouse Model of Type 2 Diabetes. Metabolites. 2021; 11(1):58. https://doi.org/10.3390/metabo11010058
Chicago/Turabian StyleSchaid, Michael D., Yanlong Zhu, Nicole E. Richardson, Chinmai Patibandla, Irene M. Ong, Rachel J. Fenske, Joshua C. Neuman, Erin Guthery, Austin Reuter, Harpreet K. Sandhu, and et al. 2021. "Systemic Metabolic Alterations Correlate with Islet-Level Prostaglandin E2 Production and Signaling Mechanisms That Predict β-Cell Dysfunction in a Mouse Model of Type 2 Diabetes" Metabolites 11, no. 1: 58. https://doi.org/10.3390/metabo11010058
APA StyleSchaid, M. D., Zhu, Y., Richardson, N. E., Patibandla, C., Ong, I. M., Fenske, R. J., Neuman, J. C., Guthery, E., Reuter, A., Sandhu, H. K., Fuller, M. H., Cox, E. D., Davis, D. B., Layden, B. T., Brasier, A. R., Lamming, D. W., Ge, Y., & Kimple, M. E. (2021). Systemic Metabolic Alterations Correlate with Islet-Level Prostaglandin E2 Production and Signaling Mechanisms That Predict β-Cell Dysfunction in a Mouse Model of Type 2 Diabetes. Metabolites, 11(1), 58. https://doi.org/10.3390/metabo11010058